Comparative sequence analysis is contributing to the identification and characterization of genomic regulatory regions with functional roles. It is effective because functionally important regions tend to evolve at a slower rate than do less important regions. The choice of species for comparative analysis is crucial: shared ancestry of a clade of species facilitates the discovery of genomic features important to that clade, whereas increased sequence divergence improves the resolution at which features can be discovered. Recent studies suggest that comparative analyses are useful for all branches of life and that, in the near future, large-scale mammalian comparative sequence analysis will provide the best approach for the comprehensive discovery of human regulatory elements.